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Twist is required for patterning the cranial nerves and maintaining the viability of mesodermal cells.

Twist encodes a basic helix-loop-helix transcription factor that is required for normal craniofacial morphogenesis in the mouse. Loss of Twist activity in the cranial mesenchyme leads to aberrant migratory behaviour of the neural crest cells, whereas Twist-deficient neural crest cells are located in an inappropriate location in the first branchial arch and display defective osteogenic and odontogenic differentiation (Soo et al. [2002] Dev. Biol. 247:251-270). Results of the present study further show that loss of Twist impacts on the patterning of the cranial ganglia and nerves but not that of the peripheral ganglia and nerves in the trunk region of the body axis. Analyses of the expression of molecular markers of early differentiation of the paraxial mesoderm and the histogenetic potency of somites of Twist(-/-) embryos reveal that Twist-deficient somites can differentiate into muscles, cartilage, and bones, albeit less prolifically. Twist function, therefore, is not essential for mesoderm differentiation. The poor growth of the Twist-deficient somites after transplantation to the ectopic site may be attributed to reduced proliferative capacity and extensive apoptosis of the paraxial mesoderm, suggesting that Twist is required for maintaining cell proliferation and viability in the mesodermal progenitors.

Animals↗

Morphological growth and thorax dimensions among Tibetan compared to Han children, adolescents and young adults born and raised at high altitude.

BACKGROUND: Studies comparing the growth of indigenous high-altitude Aymara children and children of low-altitude European descent who have been born and raised at high altitude in the Andes have provided evidence for genetically-determined differences in thorax growth, as well as for population differences in height, weight and other measures of overall size. Comparable studies now can be undertaken in Asia because of the growing number of Han Chinese who have been born and raised at high altitude on the Qinghai-Tibetan Plateau. AIM: The study compares the growth of indigenous Tibetan children and children of Han descent who have been born and raised at the same high altitudes, and under similar socio-economic conditions. SUBJECTS AND METHODS: Measurements of stature, sitting height, weight, triceps and subscapular skinfolds, upper arm muscle area, transverse chest diameter, anterio-posterior chest diameter, and chest circumference were taken on 1439 Tibetan and Han males and females between the ages of 6 and 29 years who were born and raised 3200 m, 3800 m or at 4300 m in the high altitude province of Qinghai in western China. RESULTS: Han-Tibetan differences in body size do not occur systematically for any measurement, for any age group, or for either gender; nor is there a systematic pattern of body size differences between 3200 m and 4300 m. This indicates that there are no differences in general growth between the two groups at high altitude in Qinghai, although both groups grow more slowly than urban children at low altitude in China. On the other hand, Tibetan males possess significantly deeper chests than Han males, and Tibetan females possess significantly wider chests than Han females. Tibetans of both sexes possess significantly larger chest circumferences than Han males and females. CONCLUSIONS: Although genetic similarities cannot be ruled out, comparable dietary stress is a likely explanation for the similar and slow morphological growth of Han and Tibetans at high altitude. However, Han-Tibetan differences in thorax dimensions are likely a consequence of population (genetic) differences in the response to hypoxia during growth.

Adolescent↗

Gonadal mesoderm and fat body initially follow a common developmental path in Drosophila.

During gastrulation, the Drosophila mesoderm invaginates and forms a single cell layer in close juxtaposition to the overlying ectoderm. Subsequently, particular cell types within the mesoderm are specified along the anteroposterior and dorsoventral axes. The exact developmental pathways that guide the specification of different cell types within the mesoderm are not well understood. We have analyzed the developmental relationship between two mesodermal tissues in the Drosophila embryo, the gonadal mesoderm and the fat body. Both tissues arise from lateral mesoderm within the eve domain. Whereas in the eve domain of parasegments 10-12 gonadal mesoderm develops from dorsolateral mesoderm and fat body from ventrolateral mesoderm, in parasegments 4-9 only fat body is specified. Our results demonstrate that the cell fate decision between gonadal mesoderm and fat body identity within dorsolateral mesoderm along the anteroposterior axis is determined by the combined actions of genes including abdA, AbdB and srp; while srp promotes fat body development, abdA allows gonadal mesoderm to develop by repressing srp function. Furthermore, we present evidence from genetic analysis suggesting that, before stage 10 of embryogenesis, gonadal mesoderm and the fat body have not yet been specified as different cell types, but exist as a common pool of precursor cells requiring the functions of the tin, zfh-1 and cli genes for their development.

Animals↗

Pattern formation and cell differentiation: trichomes in Arabidopsis as a genetic model system.

Arabidopsis trichomes are single-celled hairs that originate from epidermal cells and are distributed regularly on most aerial body parts. During the last decade, trichome formation in Arabidopsis has been established as a genetic and molecular model system to study various general developmental and cellular mechanisms. This review summarizes progress in the investigation of several aspects of trichome development: the spatial regulation of cell fate determination, the regulation of cell differentiation in response to exogenous signals and plant hormones, and the regulation of endoreplication, cell growth, and cell morphogenesis.

Arabidopsis↗

Movement patterns of the upper extremity and trunk before and after corrective surgery of impaired forearm rotation in patients with cerebral palsy.

The effect of surgical correction of impaired forearm rotation on associated body movement patterns was studied prospectively by comparison of preoperative and postoperative three-dimensional video analysis of the upper extremity and trunk in eight male and two female patients with hemiplegic cerebral palsy (CP; mean age 16y 2mo [SD 4y 11mo]; range 11-27y). A customized parameter, 'extrinsic forearm rotation', was used to quantify associated movements supplementing forearm rotation. After surgical correction of the pronation deformity, active forearm supination during a functional reaching task had improved by a mean of 37 degrees in combination with significantly decreased extrinsic forearm rotation by a mean of 13 degrees . In addition, an average loss of 16 degrees of active pronation in combination with increased extrinsic forearm rotation (mean 8 degrees ) was observed. On the basis of these results we conclude that successful surgical correction of a pronation deformity in patients with CP directly affects related movement patterns of the upper extremity and trunk.

Adolescent↗

Patterning the marginal zone of early ascidian embryos: localized maternal mRNA and inductive interactions.

Early animal embryos are patterned by localized egg cytoplasmic factors and cell interactions. In invertebrate chordate ascidians, larval tail muscle originates from the posterior marginal zone of the early embryo. It has recently been demonstrated that maternal macho-1 mRNA encoding transcription factor acts as a localized muscle determinant. Other mesodermal tissues such as notochord and mesenchyme are also derived from the vegetal marginal zone. In contrast, formation of these tissues requires induction from endoderm precursors at the 32-cell stage. FGF-Ras-MAPK signaling is involved in the induction of both tissues. The responsiveness for induction to notochord or mesenchyme depends on the inheritance of localized egg cytoplasmic factors. Previous studies also point to critical roles of directed signaling in polarization of induced cells and in subsequent asymmetric divisions resulting in the formation of two daughter cells with distinct fates. One cell adopts an induced fate, while the other assumes a default fate. A simple model of mesoderm patterning in ascidian embryos is proposed in comparison with that of vertebrates.

Animals↗

Regulation and function of tailless in the long germ wasp Nasonia vitripennis.

In the long germ insect Drosophila, the gene tailless acts to pattern the terminal regions of the embryo. Loss of function of this gene results in the deletion of the anterior and posterior terminal structures and the eighth abdominal segment. Drosophila tailless is activated by the maternal terminal system through Torso signaling at both poles of the embryo, with additional activation by Bicoid at the anterior. Here, we describe the expression and function of tailless in a long germ Hymenoptera, the wasp Nasonia vitripennis. Despite the morphological similarities in the mode of development of these two insects, we find major differences in the regulation and function of tailless between Nasonia and Drosophila. In contrast to the fly, Nasonia tll appears to rely on otd for its activation at both poles. In addition, the anterior domain of Nasonia tll appears to have little or no segmental patterning function, while the posterior tll domain has a much more extensive patterning role than its Drosophila counterpart.

Animals↗

The recombinant limb as a model for the study of limb patterning, and its application to muscle development.

The recombinant limb is a model system that has proved fruitful for analyzing epithelial-mesenchymal interactions and understanding the functional properties of the components of the limb bud. Here we present an overview of some of the insights obtained through the use of this technique. Among these are the understanding that fore or hind limb identity is inherent to the limb bud mesoderm, that the apical ectodermal ridge (AER) is a permissive signaling center and that the limb bud ectoderm plays a central role in the control of dorsoventral polarity. Recombinant limb studies have also allowed the identification of the affected tissue component in several limb mutants. More recently this model has been applied to the study of regulation of gene expressions related to patterning. In this report we use recombinant limbs to analyze pattering of the Pax3 expressing limb muscle cell lineage in the early stages of limb development. In recombinant limbs made without the zone of polarizing activity (ZPA), myoblasts appear intermingled with other mesodermal cells at the beginning of the recombinant limb development. Rapidly thereafter, the muscle precursors segregate and organize around the central forming chondrogenic core of the recombinant. Although this segregation is reminiscent of that occurring during normal development, the myoblasts in the recombinant fail to proliferate appropriately and also fail to migrate distally. Consequently, the muscle pattern in the recombinant limb is defective indicating that normal patterning cues are absent. However, recombinant limbs polarized with a ZPA exhibited a larger mass of muscle cells and a more normal morphogenesis, supporting a role for this signaling center in limb muscle development. Finally, we have ruled out host somite contributions to recombinant limbs by grafting chick recombinant limbs to quail hosts. This initial report demonstrates the value of the recombinant limb model system for dissecting the environmental cues required for normal muscle limb patterning.

Animals↗

Primitive streak formation in mice is preceded by localized activation of Brachyury and Wnt3.

The prevalent model for the generation of axial polarity in mouse embryos proposes that a radial to a linear transition in the expression of primitive streak markers precedes the formation of the primitive streak on one side of the epiblast. This model contrasts with the models of mesoderm formation in other vertebrates as it suggests that the primitive streak is initially established in a radial pattern rather than a localized region of the epiblast. Here, we examine the proposed correlation between the expression of Brachyury and Wnt3, two genes reported as expressed radially in the proximal epiblast, with the movements of proximal anterior epiblast cells at stages leading to the formation of the primitive streak. Our results reveal that neither Brachyury nor Wnt3 forms a ring of expression in the proximal epiblast as previously thought. In embryos dissected between 5.5 and 6.5 dpc, Brachyury is first expressed in the distal extra-embryonic ectoderm and subsequently on one side of the epiblast. Wnt3 expression is evident first in the posterior visceral endoderm of 5.5 dpc embryos and later in the posterior epiblast. Lineage analysis shows that the movements of the proximal epiblast do not restrict Brachyury expression to the posterior epiblast. Our data suggest a model whereby the localized expression of these genes in the posterior epiblast, and hence the formation of the primitive streak, is the result of local cell-cell interactions in the future posterior portion of the egg cylinder rather than regionalization of a radial pattern of expression in proximal epiblast cells.

Animals↗

Gli2 and Gli3 play distinct roles in the dorsoventral patterning of the mouse hindbrain.

Sonic Hedgehog (Shh) signaling plays a critical role during dorsoventral (DV) patterning of the developing neural tube by modulating the expression of neural patterning genes. Overlapping activator functions of Gli2 and Gli3 have been shown to be required for motoneuron development and correct neural patterning in the ventral spinal cord. However, the role of Gli2 and Gli3 in ventral hindbrain development is unclear. In this paper, we have examined DV patterning of the hindbrain of Shh(-/-), Gli2(-/-) and Gli3(-/-) embryos, and found that the respective role of Gli2 and Gli3 is not only different between the hindbrain and spinal cord, but also at distinct rostrocaudal levels of the hindbrain. Remarkably, the anterior hindbrain of Gli2(-/-) embryos displays ventral patterning defects as severe as those observed in Shh(-/-) embryos suggesting that, unlike in the spinal cord and posterior hindbrain, Gli3 cannot compensate for the loss of Gli2 activator function in Shh-dependent ventral patterning of the anterior hindbrain. Loss of Gli3 also results in a distinct patterning defect in the anterior hindbrain, including dorsal expansion of Nkx6.1 expression. Furthermore, we demonstrate that ventral patterning of rhombomere 4 is less affected by loss of Gli2 function revealing a different requirement for Gli proteins in this rhombomere. Taken together, these observations indicate that Gli2 and Gli3 perform rhombomere-specific function during DV patterning of the hindbrain.

Animals↗

Evolutionary flexibility of pair-rule patterning revealed by functional analysis of secondary pair-rule genes, paired and sloppy-paired in the short-germ insect, Tribolium castaneum.

In the Drosophila segmentation hierarchy, periodic expression of pair-rule genes translates gradients of regional information from maternal and gap genes into the segmental expression of segment polarity genes. In Tribolium, homologs of almost all the eight canonical Drosophila pair-rule genes are expressed in pair-rule domains, but only five have pair-rule functions. even-skipped, runt and odd-skipped act as primary pair-rule genes, while the functions of paired (prd) and sloppy-paired (slp) are secondary. Since secondary pair-rule genes directly regulate segment polarity genes in Drosophila, we analyzed Tc-prd and Tc-slp to determine the extent to which this paradigm is conserved in Tribolium. We found that the role of prd is conserved between Drosophila and Tribolium; it is required in both insects to activate engrailed in odd-numbered parasegments and wingless (wg) in even-numbered parasegments. Similarly, slp is required to activate wg in alternate parasegments and to maintain the remaining wg stripes in both insects. However, the parasegmental register for Tc-slp is opposite that of Drosophila slp1. Thus, while prd is functionally conserved, the fact that the register of slp function has evolved differently in the lineages leading to Drosophila and Tribolium reveals an unprecedented flexibility in pair-rule patterning.

Amino Acid Sequence↗

Role and distribution of retinoic acid during CNS development.

Retinoic acid (RA), the biologically active derivative of vitamin A, induces a variety of embryonal carcinoma and neuroblastoma cell lines to differentiate into neurons. The molecular events underlying this process are reviewed with a view to determining whether these data can lead to a better understanding of the normal process of neuronal differentiation during development. Several transcription factors, intracellular signaling molecules, cytoplasmic proteins, and extracellular molecules are shown to be necessary and sufficient for RA-induced differentiation. The evidence that RA is an endogenous component of the developing central nervous system (CNS) is then reviewed, data which include high-pressure liquid chromotography (HPLC) measurements, reporter systems and the distribution of the enzymes that synthesize RA. The latter is particularly relevant to whether RA signals in a paracrine fashion on adjacent tissues or whether it acts in an autocrine manner on cells that synthesize it. It seems that a paracrine system may operate to begin early patterning events within the developing CNS from adjacent somites and later within the CNS itself to induce subsets of neurons. The distribution of retinoid-binding proteins, retinoid receptors, and RA-synthesizing enzymes is described as well as the effects of knockouts of these genes. Finally, the effects of a deficiency and an excess of RA on the developing CNS are described from the point of view of patterning the CNS, where it seems that the hindbrain is the most susceptible part of the CNS to altered levels of RA or RA receptors and also from the point of view of neuronal differentiation where, as in the case of embryonal carcinoma (EC) cells, RA promotes neuronal differentiation. The crucial roles played by certain genes, particularly the Hox genes in RA-induced patterning processes, are also emphasized.

Alcohol Dehydrogenase↗

Coordinate expression of Fgf8, Otx2, Bmp4, and Shh in the rostral prosencephalon during development of the telencephalic and optic vesicles.

Previous studies suggest that Fgf8 has a key role in regulating vertebrate development. In the rostral head of the embryonic chicken, there are increasing numbers of separate Fgf8 domains; these are present in tissues that appear to have previously expressed Otx2. As Fgf8 expression becomes established, Otx2 expression weakens, but remains in cells abutting the Fgf8 expression domain. These Fgf8 expression domains are closely associated with tissues expressing Bmp4 and Shh. Based on analogy with the embryonic limb, we suggest that Fgf8, Bmp4 and Shh function together in patterning regions of the embryonic head. Gene expression changes are particularly prominent in 14-21 somite stage embryos in the rostral forebrain, during early morphogenesis of the telencephalic and optic vesicles, when several new interfaces of Fgf8, Bmp4 and Shh are generated. To gain insights into the functions of fibroblast growth factor 8 (FGF8) in the embryonic forebrain, we studied the effects of implanting beads containing this protein in the dorsal prosencephalon of embryonic day 2 chicken embryos. Ectopic FGF8 had profound effects on morphogenesis of the telencephalic and optic vesicles. It disrupted formation of the optic stalk and caused a transformation of the pigment epithelium into neural retina. Within the telencephalon, FGF8 beads frequently induced a sulcus that had features of an ectopic rostral midline. The sulcus separated the telencephalon into rostral and caudal vesicles. Furthermore, we present evidence that FGF8 can regulate regionalization of the prosencephalon through inhibition of Otx2 and Emx2 expression. Thus, these experiments provide evidence that FGF8 can regulate both morphogenesis and patterning of the rostral prosencephalon (telencephalic and optic vesicles). FGF8 beads can induce midline properties (e.g. a sulcus) and can modulate the specification and differentiation of adjacent tissues. We suggest that some of these effects are through regulating the expression of homeobox genes (Otx2 and Emx2) that are known to participate in forebrain patterning.

Age Factors↗

Fibroblast growth factor signaling is required for the proliferation and patterning of progenitor cells in the developing anterior pituitary.

The proliferation and patterning of progenitor cells in the anterior pituitary require signals derived from the neuroepithelium of the juxtaposed infundibulum. The infundibulum expresses Fibroblast growth factor (Fgf) 8 and Fgf 18, and FGFs can mimic some of the activities of the infundibulum. The requirement for FGF signaling during growth and patterning of the anterior pituitary has not, however, been established. By blocking FGF receptor signaling in explants of the anterior pituitary cultured in vitro we provide evidence that FGF signaling derived from the infundibulum is required for the proliferation and patterning of progenitor cells in the anterior pituitary.

Animals↗

Patterning centers, regulatory genes and extrinsic mechanisms controlling arealization of the neocortex.

The adult mammalian neocortex, the major region of the cerebral cortex, is divided into functionally specialized areas, defined by distinct architecture and axonal connections. Extrinsic influences, such as thalamocortical input, and genetic regulation, intrinsic to the dorsal telencephalon, control the gradual emergence of area-specific properties during development. Major recent advances in this field include: the first demonstration of the genetic regulation of arealization, implicating the transcription factors Emx2 and Pax6 in the direct control of area identities; and the demonstration of the potential role of the signaling protein, fibroblast growth factor 8, in the early patterning of arealization genes, such as Emx2.

Animals↗

Flamingo controls the planar polarity of sensory bristles and asymmetric division of sensory organ precursors in Drosophila.

The sensory bristles of the fruit fly Drosophila are organized in a polarized fashion such that bristles on the thorax point posteriorly. These bristles are derived from asymmetric division of sensory organ precursors (SOPs). The Numb protein, which is localized asymmetrically in a cortical crescent in each SOP, segregates into only one of the two daughter cells during cell division, thereby conferring distinct fates to the daughter cells [1] [2]. In neuroblasts, establishment of apical-basal polarity by the protein Inscuteable is crucial for orienting asymmetric division, but this is not the case for division of SOPs [3]. Instead, the Frizzled (Fz) protein mediates a planar polarity signal that controls the anteroposteriorly oriented first division (pl) of SOPs [4]. Here, we report that Flamingo (Fmi), a seven-transmembrane cadherin [5], controls the planar polarity of sensory bristles and the orientation of the SOP pl division. Both the loss of function and overexpression of fmi disrupted bristle polarity. During mitosis of the SOP, the axis of the pl division and the positioning of the Numb crescent were randomized in the absence of Fmi activity. Overexpression of Fmi and Fz caused similar effects. The dependence of proper Fmi localization on Fz activity suggests that Fmi functions downstream of Fz in controlling planar polarity. We also present evidence suggesting that Fz also functions in the Wingless pathway to pattern sensory organs.

Animals↗

Non-linear signaling for pattern formation?

Developmental pathways are often simplified as linear cascades of gene activation caused by initial signaling events. Recent data, however, support a more complex view in which non-linear responses to signals are important for pattern formation. First, a positive feedback loop may regulate cellular patterning in the Arabidopsis epidermis. Second, an asymmetric auxin distribution that organizes pattern in the distal root tip may be established by positive feedback.

Arabidopsis↗

All mouse ventral spinal cord patterning by hedgehog is Gli dependent and involves an activator function of Gli3.

An important question is how the gradient of Hedgehog is interpreted by cells at the level of the Gli transcription factors. The full range of Gli activity and its dependence on Hh have not been determined, although the Gli2 activator and Gli3 repressor have been implicated. Using the spinal cord as a model system, we demonstrate that Gli3 can transduce Hedgehog signaling as an activator. All expression of the Hh target gene Gli1 is dependent on both Gli2 and Gli3. Unlike Gli2, however, Gli3 requires endogenous Gli1 for induction of floor plate and V3 interneurons. Strikingly, embryos lacking all Gli function develop motor neurons and three ventral interneuron subtypes, similar to embryos lacking Hh signaling and Gli3. Therefore, in the spinal cord all Hh signaling is Gli dependent. Furthermore, a combination of Gli2 and Gli3 is required to regulate motor neuron development and spatial patterning of ventral spinal cord progenitors.

Animals↗